A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier:
NCT00623831
First received: February 4, 2008
Last updated: August 9, 2013
Last verified: August 2013
  Purpose

The purpose of the study is:

  • to determine the safety profile of the Mixed Bacteria Vaccine (MBV) and identify the dose of MBV that increases body temperature to 38 -39.5 °C,
  • to evaluate the effect of subcutaneous administrations of MBV on the immunological response of patients suffering from malignant tumors that express the NY-ESO-1 antigen.

It is not known if MBV will be of benefit to the patient. Ideally, the MBV should strengthen the immune system against the tumor but there is the possibility of no direct benefit to the study participants. It is anticipated that the knowledge gained will be of benefit to other cancer patients in the future.

This is a phase 1, open label, multiple dosing, single arm study. Each patient will be enrolled to receive MBV subcutaneously at the starting dose of 250 EU (1 µL) twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose will be escalated in each patient to the MBV dose level that elicits a body temperature of 38C -39.5C or up to the maximum dose level 8. Once the desired pyrogenic effect is reached, patients will then be given MBV twice weekly for 4 doses at the pyrogenic dose level. For patients not achieving the desired pyrogenic effect at dose level 8, no additional MBV will be administered.

From the Amendment 3, a second cohort of four patients was planned to receive dose level 6 (60,800 EU) twice weekly over a period of 6 weeks. Injections were administered intralesional (if applicable), and subcutaneously if intralesional drug administration was not possible. No dose escalation was planned. If a fever of 39.5°C - 40°C was observed, the patient's dose was adjusted to dose level 5 (20,300 EU (81 μl)).


Condition Intervention Phase
Melanoma
Sarcoma
Gastrointestinal Stromal Tumor (GIST)
Head and Neck Cancer
Transitional Cell Carcinoma
Prostate Cancer
Ovarian Carcinoma
Esophageal Cancer
Breast Cancer
Biological: Mixed Bacterial Vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen.

Resource links provided by NLM:


Further study details as provided by Ludwig Institute for Cancer Research:

Primary Outcome Measures:
  • Toxicities and adverse events defined by National Cancer Institute Common Terminology Criteria for Adverse Events. [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
  • Dose level(s) of MBV eliciting body temperature increase to 38 °C -39.5 °C. [ Time Frame: Weeks 1-6 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • NY-ESO-1 specific immune responses [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]

    NY-ESO-1 specific immune responses evaluated by:

    • Humoral immunity - antibody measured by ELISA,
    • Cellular immunity- CD8+ T-cell and CD4+ T-cell measured by ELISPOT.

  • Tumor response as defined by RECIST [ Time Frame: Duration of Study ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: May 2007
Study Completion Date: May 2013
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MBV from 250 to 547,000 EU (Arm 1)
Subjects of Arm 1 received MBV subcutaneously at the starting dose of 250 EU twice weekly, dose escalating for the next administrations in the absence of a dose-limiting toxicity (DLT) to the MBV dose level that elicited a body temperature of 38 °C - 39.5 °C or up to the maximum dose of 547,000 EU (level 8). The pyrogenic dose was determined to be 60,800 EU (dose level 6).
Biological: Mixed Bacterial Vaccine

Each patient of the arm 1 received Mixed Bacterial Vaccine (MBV) subcutaneously at the starting dose of 250 EU twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose was escalated in each patient to the MBV dose level that elicited a body temperature of 38C -39.5C or up to the maximum dose level 8.

Each patient of the arm 2 received Mixed Bacterial Vaccine (MBV) at the fixed pyrogenic dose level 6 (60,800 EU).

Other Name: MBV
Experimental: MBV, fixed dose 60,800 EU (Arm 2)
Arm 2 enrolled 4 patients to receive MBV at the fixed pyrogenic dose level 6 (60,800 EU).
Biological: Mixed Bacterial Vaccine

Each patient of the arm 1 received Mixed Bacterial Vaccine (MBV) subcutaneously at the starting dose of 250 EU twice weekly. In the absence of a dose-limiting toxicity (DLT), the MBV dose was escalated in each patient to the MBV dose level that elicited a body temperature of 38C -39.5C or up to the maximum dose level 8.

Each patient of the arm 2 received Mixed Bacterial Vaccine (MBV) at the fixed pyrogenic dose level 6 (60,800 EU).

Other Name: MBV

Detailed Description:

Vaccination will be administered twice weekly on Monday and Thursday of each week. During each vaccination clinic visit, patients will be observed up to 6 hours post vaccination and vital signs will be measured hourly. At baseline, and throughout the study period, patients will be assessed for NY-ESO-1 specific humoral and cellular immunity, chemistry, hematology and cytokine analysis for IL-1, IL-6, IFNgamma, and TNF-alpha. Toxicity assessments will be made throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed metastatic melanoma, head and neck cancer, transitional cell carcinoma, sarcoma, GIST (gastrointestinal stroma tumor) or prostate cancer
  • Tumor expression of 1) NY-ESO-1 by reverse transcriptase and polymerase chain reaction (RT-PCR) analysis (see Appendix 1), preferably, or immunohistochemistry (20);
  • Expected survival of at least 6 months.
  • Karnofsky performance scale >/-70 %.
  • Fully recovered from surgery.
  • Declined, intolerated or completed standard therapy defined as following for each tumor entity:

    • Melanoma- Resistance or intolerance to Dacarbazine.
    • Sarcoma-Resistance or intolerance to Anthracyclines and to one Platinum containing chemotherapy regimen, no indication for irradiation.
    • GIST (gastrointestinal stroma tumor)- Failure or intolerance of Imatinib and Sunitinib
    • Head and Neck Cancer -No indication for irradiation, resistance or intolerance to platinum containing chemotherapy.
    • Transitional Cell Carcinoma - Resistance or intolerance to Cisplatin combined with Gemcitabine
    • Prostate Cancer- Failure of antihormonal treatment and resistance or intolerance to Docetaxel
    • Ovarian Carcinoma - failure of standard chemotherapy consisting of a platinum agent combined with a taxane and of an anthracycline.
    • Esophageal Cancer - failure of standard chemotherapy consisting of a platinum agent.
    • Breast Cancer- failure or intolerance of standard first, second and third line chemotherapy consisting of a taxane, anthracycline. No indication or resistance to standard antihormonal treatment. No indication or resistance to HER-2 NEU targeted therapy. No indication or resistance to irradiation and/or surgery.
  • Within the last 2 weeks prior to study day 1, vital laboratory parameters should be within normal range, except for the following laboratory parameters, which should be within the ranges specified:

    • Absolute neutrophil count (ANC) >/- 1,000/mm3
    • Platelets >/-75,000/mm3
    • Creatinine </- 2 mg/dL
    • ALT, AST </- 5 x ULN
    • Alk Phos and total bilirubin </- 2.5 x ULN
  • Age ≥ 18 years
  • Able and willing to give valid written informed consent

Exclusion Criteria:

  • Clinically significant heart disease (NYHA Class III or IV).
  • Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
  • Patients with serious intercurrent illness, requiring hospitalization.
  • Known HIV positivity
  • Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of study agent (6 weeks for nitrosoureas).
  • Known autoimmune disease (RA, SLE), as these conditions might interfere with the evaluation of the induced immune response. Patients with vitiligo or melanoma-associated hypopigmentation are not excluded.
  • Chronic use of immunosuppressive drugs such as systemic corticosteroids.
  • Other malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ.
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability for immunological and clinical follow-up assessments.
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent.
  • Pregnancy or breastfeeding.
  • Women of childbearing potential: Refusal or inability to use effective means of contraception.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623831

Locations
Germany
Krankenhaus Nordwest
Frankfurt, Germany
Sponsors and Collaborators
Ludwig Institute for Cancer Research
Investigators
Principal Investigator: Elke Jaeger, Prof.Dr. med Krankenhaus Nordwest
  More Information

No publications provided

Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT00623831     History of Changes
Other Study ID Numbers: LUD2005-003, 2006-002015-27
Study First Received: February 4, 2008
Last Updated: August 9, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Ludwig Institute for Cancer Research:
MBV
Mixed Bacterial Vaccine
NY-ESO-1

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Esophageal Neoplasms
Head and Neck Neoplasms
Melanoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Prostatic Neoplasms
Gastrointestinal Stromal Tumors
Sarcoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on August 21, 2014